Mucofilm: a nexus for phage-microbiome interactions in gut ecology

The human gut is a dynamic ecosystem where bacteriophages (phages) and bacteria interact within a complex mucosal environment. Here, we introduce the concept of mucofilm, a hybrid matrix composed of mucus produced by host cells and bacterial biofilm, as a unified ecological niche in the gut while also recognizing its relevance to other mucus-covered surfaces. Traditionally treated as separate entities, mucus and biofilm are in fact deeply interwoven, forming a complex environment that shapes microbial interactions, phage dynamics, and host responses. We question whether traditional knowledge about phage-biofilm interactions is transferable to mucofilm, and we therefore believe that recognizing mucofilm as a distinct structure is essential for understanding how phages interact with the gut microbiome, influencing microbial resilience, diversity, and immune modulation. This commentary challenges conventional compartmentalization and highlights the need to consider mucofilm as a single, integrated system when designing microbiome and phage-related studies. By doing so, we can better predict microbial behavior and improve therapeutic strategies targeting gut-associated diseases.